ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 52 P19 | DOI: 10.1530/endoabs.52.P19

Mixed Adeno-Neuroendocrine Carcinoma (MANEC): a multicentre retrospective study

Melissa Frizziero1, Xin Wang2, Bipasha Chakrabarty3, Alexa Childs4, Tu Vinh Luong5, Thomas Walter6, Mohid S. Khan7, Meleri Morgan8, Adam Christian8, Mona Elshafie9, Tahir Shah10, Paul Fulford11, Annamaria Minicozzi11, Wasat Mansoor1, Tim Meyer4,12, Richard A. Hubner1, Juan W. Valle1,13 & Mairéad G. McNamara1,13


1Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; 2Department of Analytics and Development, The Christie NHS Foundation Trust, Manchester, UK; 3Department of Pathology, The Christie NHS Foundation Trust, Manchester, UK; 4Department of Medical Oncology, Royal Free London NHS Foundation Trust, London, UK; 5Department of Histopathology, Royal Free London NHS Foundation Trust, London, UK; 6Department of Gastroenterology and Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France; 7Department of Gastroenterology, Cardiff & Vale University Health Board, University Hospital of Wales, Cardiff, UK; 8Department of Cellular Pathology, Cardiff & Vale University Health Board, University Hospital of Wales, Cardiff, UK; 9Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 10Department of Hepatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 11Department of Surgical Oncology, The Christie NHS Foundation Trust, Manchester, UK; 12UCL Cancer Institute, University College London, London, UK; 13Division of Cancer Sciences, University of Manchester, Manchester, UK.


Introduction: MANEC is a rare diagnosis and little is known on its epidemiology/prognosis/management.

Methods: Demographic/clinical-pathological/survival data of patients with a diagnosis of MANEC (2010 WHO criteria) from five European centres were retrospectively reviewed.

Results: Sixty-six patients were identified (09/80–07/17); median age: 62.5 years (range 34–89); male: 66.7%; ECOG-PS 0-1: 59%; primary tumours from: small/large bowel 62.1%, oesophagus/stomach 22.7%, pancreas/biliary tract 13.6%, unknown 1.5%; adult-comorbidity-evaluation (ACE)-27 score 0: 36.4%. The NE component (predominant histology in 58.1% of 43 cases where this information was available) was poorly-differentiated (PD) in 80.3%, with a median Ki-67 value of 70% (95%-Confidence-Interval (CI): 60–73.6). Most frequently expressed IHC markers were: synaptophysin (87.9%), chromogranin-A (CgA) (54.5%) and CDX2 (48.5%). Histology from recurrent/metastatic sites (14 patients) was PD-NE in 71.4%. Median follow-up time was 11.5 months (mo). Of 34 (51.5%) patients with localised-stage (LA) disease, 91.2% had curative surgery (22.5% had neoadjuvant chemo-radiotherapy (CT-RT), 29% had adjuvant or peri-operative CT), 5.9% had definitive CT-RT and 2.9% had unknown management; 77.4% recurred. Fifty-four (81.8%) patients were treated for advanced-stage (adv) disease: 50% had platinum-based CT, 5.5% irinotecan-based CT, 1.8% gemcitabine, 1.8% 5-fluorouracil/leucovorin, 3.7% unknown CT regimen, 1.8% CT-RT, 1.8% RT, 24% best-supportive-care (BSC), and 9.25% unknown management. Median overall-survival (OS) for all patients was 16.2 mo (95%-CI 12.1–21). Median recurrence-free-survival and OS in patients with LA disease were 12.9 mo (95%-CI 6.7–21) and 21 mo (95%-CI 14.57–35). Median progression-free-survival (PFS) and OS in patients with adv disease were 4.9 mo (95%CI 3.5–7.2) and 14.6 mo (95%CI 9.6–19.4). On univariable analysis, age <70 years and ACE-27 score 0 (vs≥1) were prognostic for better OS (both P<0.05); IHC negativity for CgA and first-line active treatment (vsBSC) were prognostic for better PFS (both P<0.05).

Conclusion: This is one of the largest series of MANEC in current literature. PD-NE is predominant in both primary tumours and recurrent/metastatic sites. Survival outcomes are poor. Curative surgery is the preferred choice for LA patients. Platinum-based CT is the most frequently offered strategy in the adv setting.